Diet patterns and the incidence of age-related macular degeneration in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly. OBJECTIVE: This study aimed to determine the association between dietary patterns and food groups (used to make them) with the 18-year incidence of AMD. METHODS: ARIC (Atherosclerosis Risk in Communities) participants who showed change in AMD lesions between retinal photographs taken at visit 3 and visit 5 were graded side by side to determine incident AMD (any=144; early=117; late=27). A 66-line item food frequency questionnaire, administered at visit 1 and visit 3, was used to identify 29 food groups. Principal component analysis was used to derive dietary patterns from average food group servings. Logistic regression was used to estimate ORs and 95% CIs for incident AMD (any, early and late) by tertiles of dietary pattern scores, adjusted for age, race, education, total calories and smoking status. P-trend was estimated using continuous scores. RESULTS: Western (unhealthy) and Prudent (healthy) dietary patterns were identified. No significant associations were observed between either dietary pattern and incident any or incident early AMD. However, a threefold higher incidence of late AMD was observed among participants with a Western pattern score above, as compared with below, the median (OR=3.44 (95% CI 1.33 to 8.87), p-trend=0.014). The risk of developing late AMD was decreased, but not statistically significant, among participants with a Prudent pattern score above, as compared with below, the median (OR=0.51 (95% CI 0.22 to 1.18), p-trend=0.054). CONCLUSIONS: Diet patterns were not significantly associated with incident any or incident early AMD. However, consumption of a Western pattern diet may be a risk factor for development of late AMD.

An Association Between Large Optic Nerve Cupping and Cognitive Function.

PURPOSE: To determine if a larger cup-to-disc ratio is associated with poor cognitive function in postmenopausal women without glaucoma or ocular hypertension. METHODS: We used data from the Women's Health Initiative (WHI) hormone trial, originally designed to test effects of hormone therapy (HT) on various health outcomes. Large cup-to-disc ratio was defined as greater than 0.6 in either eye based on stereoscopic optic nerve photographs. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) in the WHI Memory Study. Exclusions were no information on optic nerve grading; no 3MSE scores at the time of the eye examination, ocular hypertension (intraocular pressure >23 mm Hg, Goldmann applanation tonometry), or glaucoma medication use. A generalized linear model for log-transformed 3MSE scores was used for determining the association between large cup-to-disc ratio and 3MSE scores, adjusting for age, race, diabetes, body mass index, cardiovascular disease, smoking, HT randomization, education, and diabetic retinopathy. RESULTS: Analyses included 1636 women (mean age ± standard deviation, 69.57 ± 3.64 years; 90.39% white). Of those, 122 women had large cup-to-disc ratio. The mean 3MSE scores in women with vs without large cup-to-disc ratio were 95.4 ± 6 vs 96.6 ± 5. In the adjusted model, women with large cup-to-disc ratio had statistically significantly lower 3MSE scores, compared with those without large cup-to-disc ratio, yielding the predicted mean difference in 3MSE scores of 0.75 with a standard error of 0.05 units (P = .04). CONCLUSIONS: Postmenopausal women who had large cup-to-disc ratio without glaucoma or ocular hypertension exhibited lower global cognitive function. Further investigation is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Serum 25-Hydroxyvitamin D Concentrations and Incidence of Age-Related Macular Degeneration: The Atherosclerosis Risk in Communities Study.

Purpose: To investigate the association between serum 25-hydroxyvitamin D (25[OH]D) concentrations at visit 2 (1990-1992) and the 18-year incidence of age-related macular degeneration (AMD) between visit 3 (1993-1995) and visit 5 (2011-2013). Methods: This prospective analysis was conducted in a subset of participants (n = 1225) from the Atherosclerosis Risk in Communities Study. We evaluated the incidence of any, early, and late AMD from visit 3 to 5. The 25(OH)D concentrations were assessed in 2012-2013 by using stored serum from visit 2. Retinal fundus photographs taken at both visits were graded side by side to determine the incidence of AMD. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for incident AMD outcomes during 18 years of follow-up (1993-1995 to 2011-2013) by tertile of 25(OH)D adjusted for age, race, and smoking status. P for linear trend was estimated by using continuous 25(OH)D concentrations. Sensitivity analyses applied inverse probability weights to account for selection to have eye photographs, death, and loss to follow-up. Results: There was a decreased odds of any incident AMD (n = 139) and large, soft drusen (n = 80) in 25(OH)D tertile 3 versus 1, with OR (95% CI) = 0.57 (0.36-0.90), P trend = 0.11 and with 0.52 (0.28-0.93), P trend = 0.18, respectively. Applying sampling weights attenuated these results to 0.66 (0.38-1.16), P trend = 0.32 (any incident AMD) and 0.54 (0.27-1.09), P trend = 0.36 (large, soft drusen), respectively, suggesting these associations may be biased by loss to follow-up and sampling for retinal photographs at visit 5. No statistically significant results were observed with pigmentary abnormalities (n = 46) or incident late AMD (n = 26). Conclusions: High 25(OH)D concentrations, approximately >70 nM, may be associated with decreased odds of incident early AMD.

Neural dysfunction and retinopathy in persons with type 1 diabetes.

OBJECTIVE: To determine associations of microvascular and neuropathic complications of diabetes cross-sectionally and longitudinally in persons with long-term type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Persons receiving care for T1D in South Central Wisconsin were identified in 1979-1980 and examined approximately every 5 years. Associations between neuropathic and microvascular complications were examined at most prior visits, when information on several neuropathic complications was collected. Temporal relationships were examined by modeling incidence between examinations across the visits. RESULTS: Adjusting for duration of diabetes, glycated hemoglobin, and systolic blood pressure, the following were cross-sectionally associated with prevalent PDR (proliferative diabetic retinopathy): the presence of sensory neuropathy (SN) as reported at each Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) examination (odds ratio (OR) = 2.76, confidence interval (CI) = 1.71, 4.48) and the heartrate variability measures RMSD (square root of the mean of squared differences of successive RR intervals) (OR = 0.24, CI = 0.16, 0.37) and SDNN (standard deviation of successive RR intervals) (OR = 0.26, CI = 0.17, 0.39). Findings were similar for prevalent ME (macular edema) as assessed from spectral-domain optical coherence tomography (SD-OCT). The presence of PDR (OR = 2.13, CI = 1.63, 2.78) and ME (OR = 2.36, CI = 1.66, 3.34) were both significantly associated with incident WESDR SN. WESDR SN was associated with incident PDR (OR = 1.53, CI = 1.09, 2.15) but not incident ME (OR = 1.31, CI = 0.92, 1.87). CONCLUSIONS: Sensory neuropathy and heartrate variability were significantly associated with prevalent PDR and ME in people with long-term T1D. PDR and ME were significantly associated with incident sensory neuropathy, and sensory neuropathy was significantly associated with incident PDR. Studies using earliest detectable markers of microvascular and neurologic abnormalities are needed to determine which of the two systems 'fails' first. Such information might suggest a temporal sequence of diabetes complications.

Joint Contribution of Genetic Susceptibility and Modifiable Factors to the Progression of Age-Related Macular Degeneration over 10 Years: The Three Continent AMD Consortium Report.

PURPOSE: To assess joint effects of genetic and modifiable factors on the 10-year progression of age-related macular degeneration (AMD). DESIGN: Individual and pooled data analyses of 2 population-based cohorts. PARTICIPANTS: Blue Mountains Eye Study (BMES) and Rotterdam Study (RS) participants (n = 835). METHODS: Participants of the BMES and RS were followed up over 10 years or more. At baseline and follow-up visits, interviews using questionnaires and eye examinations with retinal photography were performed. Age-related macular degeneration was assessed by trained photographic graders and verified by retinal specialists. Genetic susceptibility to AMD meant carrying 2 or more risk alleles of the CFH or ARMS2 SNPs, or both (rs1061170 and rs10490924), relative to 0 or 1 risk allele. Discrete logistic regression models were used to investigate the joint associations of genetic susceptibility and either smoking, fish consumption, dietary intake of lutein-zeaxanthin, or combined environmental risk scores from the 3 modifiable factors with the risk of AMD progression. Odds ratios (ORs) with 95% confidence intervals (CIs) and synergy indexes are reported. MAIN OUTCOME MEASURE: Ten-year progression of AMD, categorized as any (≥1 step) or 2-step (≥2 steps) progression on the Three Continent AMD Consortium 5-step severity scale. RESULTS: Older age, the presence of AMD genetic susceptibility, and baseline AMD status were associated strongly with AMD progression (P < 0.0001). In analyses of pooled data, each additional score from the combined environmental risk scores was associated with an increased risk of 2-step progression over 10 years (OR, 1.26; 95% CI, 1.02-1.56). The copresence of AMD genetic susceptibility and combined risk score of 3 or more was associated with a substantially higher risk of 2-step progression compared with the presence of either factor alone. There was a significant synergistic effect (OR, 4.14; 95% CI, 1.07-15.95) and interaction (P = 0.025) between genetic susceptibility and environmental risk score of 3 or more. CONCLUSIONS: Among persons with AMD genetic susceptibility and pre-existing early AMD lesions, presenting with high environmental risk scores from 3 modifiable factors (smoking, infrequent consumption of fish, low lutein-zeaxanthin intake) were associated with an increased risk of 2-step progression over 10 years.

Skin Intrinsic Fluorescence and Age-Related Macular Degeneration: The Beaver Dam Eye Study.

Purpose: To determine if skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation endproducts and oxidative stress in skin is associated with AMD. Methods: SIF was measured with the SCOUT DS skin fluorescence spectrometer in a cross-sectional cohort study of 969 persons aged 68 to 102 years from the 1181 who participated in the 25-year follow-up examination in the Beaver Dam Eye Study (BDES) in 2014 to 2016. The SCOUT DS skin fluorescence spectrometer uses five light-emitting diodes, centered at 375 nm to 456 nm. AMD was assessed by grading of digital color 45° stereoscopic fundus photographs of the macula using the Wisconsin Age-Related Maculopathy grading scheme. Analyses included logistic regression with generalized estimating equations to account for correlation between the eyes of a person. Results: There were data for 1827 eyes for analyses. Early AMD was present in 22% and late AMD in 4% of the eyes. While adjusting for age, sex, smoking status, and history of cardiovascular disease, there were no significant associations of any SIF measure with any AMD or exudative AMD. SIF01 (odds ratio per 1 SD difference on the log scale, 95% confidence interval) (1.66, 1.00-2.74, P = 0.05) and SIF03 (1.81, 1.16-2.81, P = 0.008) were associated with geographic atrophy. Conclusions: There was a suggestive relationship of two SIF measures, SIF01 and SIF03, using different correction factors from the excitation centered at 375 nm, with the prevalence of geographic atrophy in the BDES. Longitudinal follow-up is indicated to assess a temporal relationship.

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report.

PURPOSE: To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. DESIGN: Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. METHODS: Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors. RESULTS: In any 5-year duration, 19-28% of unilateral any AMD cases became bilateral and 27-68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye. CONCLUSION: One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement.

Nerve Fiber Layer Thickness and Characteristics Associated with Glaucoma in Community Living Older Adults: Prelude to a Screening Trial?

PURPOSE: To examine the associations of nerve fiber layer (NFL) thickness with other ocular characteristics in older adults. METHODS: Participants in the Beaver Dam Eye Study (2008-2010) underwent spectral domain optical coherence tomography (SD-OCT) scans of the optic nerve head, imaging of optic discs, frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP), and an interview concerning their history of glaucoma and use of drops to lower eye pressure. Self-reported histories of glaucoma and the use of drops to lower eye pressure were obtained at follow-up examinations (2014-2016). RESULTS: NFL thickness measured on OCTs varied by location around the optic nerve. Age was associated with mean NFL thickness. Mean NFL was thinnest in eyes with larger cup/disc (C/D) ratios. Horizontal hemifield defects or other optic nerve-field defects were associated with thinner NFL. NFL in persons who reported taking eye drops for high intraocular pressure was thinner compared to those not taking drops. After accounting for the presence of high intraocular pressure, large C/D ratios or hemifield defects, eyes with thinner NFL in the arcades were more likely (OR = 2.3 for 30 micron thinner NFL, p = 0.04) to have incident glaucoma at examination 5 years later. CONCLUSION: Retinal NFL thickness was associated with a new history of self-reported glaucoma 5 years later. A trial testing the usefulness of NFL as part of a screening battery for predicting glaucoma in those previously undiagnosed might lead to improved case finding and, ultimately, to diminishing the risk of visual field loss.

The epidemiology of vitreoretinal interface abnormalities as detected by spectral-domain optical coherence tomography: the beaver dam eye study.

PURPOSE: To describe the prevalence and interrelationships of epiretinal membranes (ERMs), vitreomacular traction (VMT), macular cysts, paravascular cysts (PVCs), lamellar macular holes (LMHs), full-thickness macular holes (FTMHs), and visual impairment in a population-based study of older adults. DESIGN: Cross-sectional study. PARTICIPANTS: There were 1913 participants aged 63 to 102 years at the 20-year Beaver Dam Eye Study follow-up examination in 2008-2010, of whom 1540 (2980 eyes) had gradable spectral-domain optical coherence tomography (SD OCT) scans of the macula in at least 1 eye. METHODS: The presence of ERMs and other retinal lesions was determined by standardized grading of macular SD OCT scans and photographs of 3 standard fields. MAIN OUTCOME MEASURES: Epiretinal membranes, VMT, macular cysts, PVCs, LMHs, FTMHs, and visual impairment. RESULTS: By using SD OCT, the prevalence of ERMs (34.1%), VMT (1.6%), macular cysts (5.6%), PVCs (20.0%), LMHs (3.6%), and FTMHs (0.4%) was estimated. The prevalence of macular cysts (P < 0.001), ERMs (P < 0.001), and VMT (P = 0.005) increased with age; the prevalence of PVCs (P = 0.05) decreased with age; and the prevalence of LMHs was not associated with age (P = 0.70). The prevalence of macular cysts, LMHs, and ERMs was higher in eyes with a history of cataract surgery. Macular cysts and ERMs were more common in eyes with retinal diseases, such as proliferative diabetic retinopathy, retinal vein occlusion, and retinal detachment, than in eyes without these conditions. Macular cysts, ERMs, and FTMHs were associated with visual impairment. While adjusting for age and sex, macular cysts (odds ratio [OR], 3.96; P < 0.0001), PVCs (OR, 1.45, P = 0.007), LMHs (OR, 10.62; P < 0.001), VMT (OR, 2.72, P = 0.01), and visual impairment (OR, 3.23; P < 0.001) were more frequent in eyes with ERMs compared with eyes without ERMs. CONCLUSIONS: Epiretinal membranes are associated with macular cysts, PVCs, LMHs, VMT, and visual impairment. Further follow-up will allow better understanding of the natural history of ERMs and VMT and their relationships to the development of macular cysts and LMHs in the aging population.

Retinal thickness measured by spectral-domain optical coherence tomography in eyes without retinal abnormalities: the Beaver Dam Eye Study.

PURPOSE: To examine relationships of age, sex, and systemic and ocular conditions with retinal thickness measured by spectral-domain ocular coherence tomography (SD OCT) in participants without retinal disease. DESIGN: Longitudinal study. METHODS: setting: Population-based cohort. study population: Persons aged 43-86 years living in Beaver Dam, Wisconsin in 1988-1990. observation procedures: Retinal thickness was measured via SD OCT at the Beaver Dam Eye Study examination in 2008-2010. Retinal disease was determined by ophthalmoscopy, fundus photography, or SD OCT. main outcome measures: Retinal thickness from the inner limiting membrane to the Bruch membrane. RESULTS: The retina was thickest in the inner circle (mean 334.5 µm) and thinnest in the center subfield (285.4 µm). Mean retinal thickness decreased with age in the inner circle (P < .0001) and outer circle (P < .0001). Adjusting for age, eyes in men had thicker retinas than eyes in women in the center subfield (P < .001) and inner circle (P < .001). Sex, axial length/corneal curvature ratio, and peak expiratory flow rate were associated with center subfield thickness. Sex and peak expiratory flow rate were associated with retinal thickness in the inner circle. Alcohol consumption, age, axial length/corneal curvature ratio, cataract surgery, ocular perfusion pressure, and peak expiratory flow rate were associated with retinal thickness in the outer circle. CONCLUSIONS: This study provides data for retinal thickness measures in eyes of individuals aged 63 years and older without retinal disease. This information may be useful for clinical trials involving the effects of interventions on retinal thickness and for comparisons with specific retinal diseases affecting the macula.

Genetic susceptibility, dietary antioxidants, and long-term incidence of age-related macular degeneration in two populations.

OBJECTIVE: To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk. DESIGN: Pooled data analysis of population-based cohorts. PARTICIPANTS: Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). METHODS: Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], ß-carotene, and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were estimated from food frequency questionnaires. The AMD genetic risk was classified according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924) as low (no or 1 risk allele) or high (≥ 2 risk alleles). Interactions between dietary intake and genetic risk levels were assessed. Associations between dietary intake and AMD risk were assessed comparing the highest with the 2 lower intake tertiles by genetic risk subgroups using discrete logistic regression, conducted in each study separately and then using pooled data. Participants without AMD lesions at any visit were controls. We adjusted for age and sex in analyses of each cohort sample and for smoking status and study site in pooled-data analyses. MAIN OUTCOME MEASURES: All 15-year incident late AMD cases were confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS. Intergrader reproducibility was assessed in an early AMD subsample, with 86.4% agreement between BMES and RS graders, allowing for a 1-step difference on a 5-step AMD severity scale. RESULTS: In pooled data analyses, we found significant interaction between AMD genetic risk status and LZ intake (P=0.0009) but nonsignificant interactions between genetic risk status and weekly fish consumption (P=0.05) for risk of any AMD. Among participants with high genetic risk, the highest intake tertile of LZ was associated with a >20% reduced risk of early AMD, and weekly consumption of fish was associated with a 40% reduced risk of late AMD. No similar association was evident among participants with low genetic risk. No interaction was detected between ß-carotene or vitamin C and genetic risk status. CONCLUSIONS: Protection against AMD from greater LZ and fish consumption in persons with high genetic risk based on 2 major AMD genes raises the possibility of personalized preventive interventions.

Variability of measurement of retinal vessel diameters.

PURPOSE: To examine the effects of various cardiovascular, ocular, and lifestyle factors on retinal vessel diameters over short periods of time. METHODS: Subjects were invited to have photographs of their retina taken at each of three study visits. The same eye was photographed each time. The photographs were digitized and retinal vessel diameters were measured. Measurements from the retinal photographs taken consecutively (at visit 2 and visit 3), and 1, 3, and 4 weeks apart (between visits 1 and 2, 2 and 3, and 1 and 3, respectively) were compared. RESULTS: There were 63 persons who participated in all study visits and had gradable vessel measurements from all five images used in the analysis. Correlations for pairs of study visits were high, and decreased slightly with increasing length of the time interval. For consecutive photographs taken, and 1 week, 3 weeks, and 4 weeks apart, correlations were 0.95, 0.90, 0.91, and 0.86, respectively, for central retinal arteriolar equivalent (CRAE) and 0.95, 0.90, 0.91, and 0.87, respectively, for central retinal venular equivalent (CRVE). We examined the associations of blood pressure levels, smoking habits, time since last eating, exercising, consuming caffeine, and taking anti-hypertensive medication, and image focus with CRAE and CRVE. We found no consistent pattern of association of any of these characteristics with short-term changes in CRAE and CRVE. CONCLUSION: Retinal vessel diameters are stable over short intervals of time and none of the factors studied were consistently associated with change in the diameters of either vessel type.

Prediction of age-related macular degeneration in the general population: the Three Continent AMD Consortium.

PURPOSE: Prediction models for age-related macular degeneration (AMD) based on case-control studies have a tendency to overestimate risks. The aim of this study is to develop a prediction model for late AMD based on data from population-based studies. DESIGN: Three population-based studies: the Rotterdam Study (RS), the Beaver Dam Eye Study (BDES), and the Blue Mountains Eye Study (BMES) from the Three Continent AMD Consortium (3CC). PARTICIPANTS: People (n = 10,106) with gradable fundus photographs, genotype data, and follow-up data without late AMD at baseline. METHODS: Features of AMD were graded on fundus photographs using the 3CC AMD severity scale. Associations with known genetic and environmental AMD risk factors were tested using Cox proportional hazard analysis. In the RS, the prediction of AMD was estimated for multivariate models by area under receiver operating characteristic curves (AUCs). The best model was validated in the BDES and BMES, and associations of variables were re-estimated in the pooled data set. Beta coefficients were used to construct a risk score, and risk of incident late AMD was calculated using Cox proportional hazard analysis. Cumulative incident risks were estimated using Kaplan-Meier product-limit analysis. MAIN OUTCOME MEASURES: Incident late AMD determined per visit during a median follow-up period of 11.1 years with a total of 4 to 5 visits. RESULTS: Overall, 363 participants developed incident late AMD, 3378 participants developed early AMD, and 6365 participants remained free of any AMD. The highest AUC was achieved with a model including age, sex, 26 single nucleotide polymorphisms in AMD risk genes, smoking, body mass index, and baseline AMD phenotype. The AUC of this model was 0.88 in the RS, 0.85 in the BDES and BMES at validation, and 0.87 in the pooled analysis. Individuals with low-risk scores had a hazard ratio (HR) of 0.02 (95% confidence interval [CI], 0.01-0.04) to develop late AMD, and individuals with high-risk scores had an HR of 22.0 (95% CI, 15.2-31.8). Cumulative risk of incident late AMD ranged from virtually 0 to more than 65% for those with the highest risk scores. CONCLUSIONS: Our prediction model is robust and distinguishes well between those who will develop late AMD and those who will not. Estimated risks were lower in these population-based studies than in previous case-control studies.

The relationship of atherosclerosis to the 10-year cumulative incidence of age-related macular degeneration: the Beaver Dam studies.

OBJECTIVE: To describe the relationships of intima-media thickness (IMT), plaque in the carotid artery, angina, myocardial infarction (MI), and stroke to the 10-year cumulative incidence of early and late age-related macular degeneration (AMD) and progression of AMD. DESIGN: Cohort study. PARTICIPANTS: A total of 1700 persons aged 53 to 96 years who participated in both the Epidemiology of Hearing Loss Study and the Beaver Dam Eye Study in 1998-2000, with photographs gradable for AMD at 5-year (2003-2005) and 10-year (2008-2010) follow-up examinations. METHODS: The IMT and presence of plaque were assessed using B-mode ultrasonography of the carotid artery. Presence of angina, MI, and stroke were defined on the basis of a self-reported history of physician diagnosis. The presence and severity of AMD were determined by systematic grading of stereoscopic color fundus photographs. MAIN OUTCOME MEASURES: Age-related macular degeneration. RESULTS: The 10-year cumulative incidence of early AMD was 15.7%, and the 10-year cumulative incidence of late AMD was 4.0%. After adjusting for age, sex, body mass index, smoking status, age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) genotypes, and other factors, mean IMT was associated with the 10-year incidence of early AMD (odds ratio [OR] per 0.1 mm IMT, 1.11; 95% confidence interval [CI], 1.00-1.21; P = 0.03) and late AMD (OR per 0.1 mm IMT, 1.27; CI, 1.10-1.47; P = 0.001). Mean IMT was associated with the 10-year incidence of pure geographic atrophy (OR per 0.1 mm IMT, 1.31; CI, 1.05-1.64; P = 0.02) but not exudative AMD (OR per 0.1 mm IMT, 1.14; CI, 0.97-1.34; P = 0.11). Similar associations were found for maximum IMT. The number of sites with plaque was related to the incidence of late AMD (OR per 0.1 mm IMT, 2.79 for 4-6 sites vs. none; CI, 1.06-7.37; P = 0.04) but not to early AMD. A history of angina, MI, or stroke was not related to any incident AMD outcome. CONCLUSIONS: In these population-based data, carotid artery IMT and carotid plaques had a weak relationship to the incidence of late AMD that was independent of systemic and genetic risk factors. Angina, MI, and stroke were not related to AMD. It is unclear whether the carotid IMT is a risk indicator of processes affecting Bruch's membrane and the retinal pigment epithelium, or a measure of atherosclerosis affecting susceptibility to AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prevalence and characteristics of choroidal nevi: the multi-ethnic study of atherosclerosis.

OBJECTIVE: To describe the prevalence of choroidal nevi in 4 racial or ethnic groups (white, black, Hispanic, and Chinese) in the United States. DESIGN: Cross-sectional study. PARTICIPANTS: Participants of the second examination of the Multi-Ethnic Study of Atherosclerosis (MESA), involving 6176 persons 44 to 84 years of age without clinical cardiovascular disease at baseline selected from 6 United States communities. METHODS: Fundus images were taken using a 45° digital camera through dark-adapted pupils and were graded for choroidal nevi using the modified Wisconsin Age-Related Maculopathy Grading System and the Blue Mountains Eye Study protocol. MAIN OUTCOME MEASURES: Choroidal nevi. RESULTS: The overall prevalence of choroidal nevi in the whole cohort was 2.1%, with prevalences higher in whites (4.1%) than blacks (0.7%), Hispanics (1.2%), and Chinese (0.4%; P<0.001 for any differences among groups). The lowest prevalence of choroidal nevi occurred in those 75 to 84 years of age. The nevi were subfoveal in 4% of eyes with nevi and were not associated with a decrease in visual acuity. Characteristics of the nevi (size, shape, location, color, drusen on surface) did not differ among racial or ethnic groups. With the exception of associations with higher C-reactive protein levels (odds ratio [OR] per mg/dl on the logarithmic scale, 1.23; 95% confidence interval [CI], 1.06-1.43; P = 0.01) and lower systolic blood pressure (OR per 10 mmHg, 0.90; 95% CI, 0.82-0.99; P = 0.04), choroidal nevi were not associated with other potential risk factors (e.g., gender, smoking status, alcohol consumption, lipid levels, coagulation factors, or kidney disease). CONCLUSIONS: Low prevalences of choroidal nevi were found in the 4 groups participating in the MESA cohort, with whites having higher prevalence than the other racial or ethnic groups. The higher prevalence in whites than in other groups was not explained by any of the factors studied. When choroidal nevi were present, their characteristics did not differ among racial or ethnic groups. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The prevalence of macular telangiectasia type 2 in the Beaver Dam eye study.

PURPOSE: To examine the prevalence of macular telangiectasia type 2 and lesions characterizing it. DESIGN: Population-based cohort study. METHODS: setting: City and township of Beaver Dam, 1988-1990. study population: A total of 4790 people 43-86 years of age. observation procedure(s): Grading from stereoscopic fundus photographs to measure macular telangiectasia type 2. main outcome measure: Prevalent macular telangiectasia type 2. RESULTS: Macular telangiectasia type 2 was present at baseline in 0.1% of the population (95% confidence interval [CI] 0.09, 0.1). The frequencies of loss of retinal transparency, crystals in the inner retinal layers, blunted retinal vessels, localized intraretinal pigment migration in the juxtafoveolar region, and presence of yellow deposits and lamellar holes in the foveal area in those without macular telangiectasia type 2 varied from 0.06% for retinal telangiectatic vessels to 1.2% for lamellar holes. Smoking was associated with pigment clumping (odds ratio [OR] per pack year 1.02; 95% CI 1.00, 1.03; P = .02), retinal pigment epithelial (RPE) depigmentation (OR 1.02 per pack year; 95%CI 1.00, 1.04; P = .02), loss of transparency (OR 1.02 per pack year; 95% CI 1.00, 1.03; P = .008), and the presence of a yellow spot in the fovea (OR 2.24 current vs past or never smoker; 95% CI 1.29, 3.89; P = .004), but not with presence of macular telangiectasia type 2 (OR 2.72; 95% CI 0.45, 16.28; P = .27). CONCLUSIONS: The prevalence of macular telangiectasia type 2 (0.1%) is higher than previously thought. These data are useful in estimating the burden of this condition in the population. The role of smoking in the development of macular telangiectasia type 2 requires further study.

Retrodots in the lens in the Beaver Dam Eye Study cohort.

OBJECTIVE: To determine the prevalence of retrodots in the lens and the association of these lesions to age-related cataract, and to assess their association with visual impairment and contrast sensitivity. DESIGN: Longitudinal epidemiologic study. PARTICIPANTS: The Beaver Dam Eye Study cohort. METHODS: Eye examinations including grading of standard photographs of the lens and measures of visual function. MAIN OUTCOME MEASURES: Statistical associations of retrodots with nuclear, cortical, and posterior subcapsular cataracts and with incident visual impairment and impairment of contrast sensitivity. RESULTS: The prevalence of retrodots at the baseline examination increased with age from 1.68% in those 43 to 54 years of age to 31.20% in those ≥ 75 years of age. After controlling for age, there was no significant difference in the prevalence of retrodots between men and women. The odds ratio (OR) for visual impairment associated with retrodots was 2.22 (95% confidence interval [CI], 1.80-2.75) after controlling for age-related cataracts and other associated characteristics. The association with impaired contrast sensitivity was not significant. Retrodots were not significantly associated with incidence of any type of age-related cataract. The 15-year cumulative incidence of retrodots in right eyes increased with age from 9.3% in those 43 to 54 years of age to 21.1% in those ≥ 75 years of age. In addition to age, incidence of retrodots was independently associated with smoking (OR, 1.27; 95% CI, 1.04-1.56 for ever vs never smoking). CONCLUSIONS: Retrodots are frequently occurring age-related lens opacities that are associated with decreased vision independent of the presence of age-related cataract. Their incidence is associated with smoking. Further research to determine the underlying process leading to retrodots is necessary before efforts to develop preventions are undertaken.

The epidemiology of retinal reticular drusen.

PURPOSE: To describe the prevalence and 15-year cumulative incidence of and risk factors for reticular drusen. DESIGN: Population-based prospective study. METHODS: Four thousand nine hundred and twenty-six persons, 43 to 86 years of age, were included between 1988 and 1990, of whom 3,684, 2,764, and 2,119 participated in five-, 10-, and 15-year follow-up examinations, respectively, in Beaver Dam, Wisconsin. Main outcome measures included prevalence and 15-year incidence of reticular drusen determined by grading stereoscopic color fundus photographs. RESULTS: The prevalence at baseline and the 15-year cumulative incidence in either eye of reticular drusen was 0.7% and 3.0%, respectively. The 15-year incidence of reticular drusen varied with age from 0.4% in those 43 to 54 years of age to 6.6% in those 75 years or older at baseline (P < .001). In a multivariate model, while controlling for age, risk factors statistically significantly associated with increased risk of incident reticular drusen included: being female (odds ratio [OR], 2.8), current smoking (OR vs never, 1.9), less education (OR per category, 1.7), B-vitamin complex use (OR vs none, 2.5), single vitamin B (OR vs none, 2.9), history of steroid eye drops use (OR, 5.9), glaucoma (OR, 2.8), and more severe drusen type (e.g., soft indistinct drusen; OR, 1.4), whereas diabetes (OR, 0.1) at baseline was associated with decreased risk. Right eyes with reticular drusen at baseline had higher cumulative incidence of geographic atrophy (21% vs 9%) and exudative age-related macular degeneration [AMD] (20% vs 10%) compared with eyes with soft indistinct drusen. CONCLUSIONS: This population-based study documents the long-term cumulative incidence of reticular drusen and its risk factors and shows its association with a high risk of incident late AMD.

The relationship of optic disk cupping to retinal vein occlusion: the Beaver Dam Eye Study.

PURPOSE: To examine the association between optic disk cupping and retinal vein occlusion (RVO). DESIGN: Prospective epidemiologic study. METHODS: setting: Population-based prospective study in Beaver Dam, Wisconsin. study population: Adults aged 43 to 86 years at baseline (n = 4926). observation procedures: Optic disk cupping and RVO were determined from retinal photographs. A standardized medical examination and questionnaire were administered. main outcome measure: Ten-year cumulative incidence of RVO. RESULTS: There were 58 persons who developed incident RVO at 5 (n = 31) or 10 (n = 27) years after the baseline examination. Those sustaining RVO were older, had higher intraocular pressure (IOP), and were more likely to have definite or probable glaucoma at the baseline examination. The odds of having an incident RVO increased with increasing cup-to-disk ratio at baseline (odds ratio [OR] = 1.29/0.1 increase in cup-to-disk ratio, 95% confidence interval 1.07, 1.56), while controlling for age, systolic blood pressure, current smoking, diabetes status, and IOP. A similar OR was found after excluding those with glaucoma. Excluding persons with central (as opposed to branch) vein occlusion did not have a significant effect on the OR. CONCLUSION: Cup-to-disk ratio is a significant predictor of risk of incident RVO.